Psoralen plus long wavelength ultraviolet radiation(UV-A) is being investigated as a model system for clinically relevant photochemical carcinogenesis. Used experimentally for treatment of psoriasis and mycosis fungoides, psoralen plus UV-A has been found to be mutagenic in bacteria and carcinogenic in mice and humans. We have developed an in vitro assay to measure the effects of UV-A mediated psoralen-DNA binding on human lymphoid cells. Parameters monitored include the rate of DNA synthesis, induction of DNA-psoralen cross-links, induction of sister chromatid exchanges, alterations in the rate of cell proliferation and survival, and in immune reactivity. Presently we are investigating whether lymphoid cells from patients with cancer-prone genetic diseases have increased sensitivity to psoralen plus UV-A induced cell killing. These studies are aimed at understanding the mechanism of cell damage induced by psoralen plus UV-A so as to minimize the toxicity to human cells during therapy.